Antikinetoplastid SAR study in 3-nitroimidazopyridine series: Identification of a novel non-genotoxic and potent anti-T. b. brucei hit-compound with improved pharmacokinetic properties.
Animals
DNA Damage
/ drug effects
Drug Discovery
Hep G2 Cells
Humans
Imidazoles
/ chemistry
Inhibitory Concentration 50
Mice
Parasitic Sensitivity Tests
Pyridines
/ chemistry
Serum Albumin
/ metabolism
Structure-Activity Relationship
Trypanocidal Agents
/ chemistry
Trypanosoma brucei brucei
/ drug effects
Imidazo[1,2-a]pyridine
Kinetoplastids
Nitroaromatic
Nitroreductases
Redox potentials
SARs
Journal
European journal of medicinal chemistry
ISSN: 1768-3254
Titre abrégé: Eur J Med Chem
Pays: France
ID NLM: 0420510
Informations de publication
Date de publication:
15 Nov 2020
15 Nov 2020
Historique:
received:
28
05
2020
revised:
13
07
2020
accepted:
14
07
2020
pubmed:
17
8
2020
medline:
20
4
2021
entrez:
16
8
2020
Statut:
ppublish
Résumé
To study the antikinetoplastid 3-nitroimidazo[1,2-a]pyridine pharmacophore, a structure-activity relationship study was conducted through the synthesis of 26 original derivatives and their in vitro evaluation on both Leishmania spp and Trypanosoma brucei brucei. This SAR study showed that the antitrypanosomal pharmacophore was less restrictive than the antileishmanial one and highlighted positions 2, 6 and 8 of the imidazopyridine ring as key modulation points. None of the synthesized compounds allowed improvement in antileishmanial activity, compared to previous hit molecules in the series. Nevertheless, compound 8, the best antitrypanosomal molecule in this series (EC
Identifiants
pubmed: 32795774
pii: S0223-5234(20)30640-1
doi: 10.1016/j.ejmech.2020.112668
pii:
doi:
Substances chimiques
Imidazoles
0
Pyridines
0
Serum Albumin
0
Trypanocidal Agents
0
imidazopyridine
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
112668Informations de copyright
Copyright © 2020 Elsevier Masson SAS. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.